Peritumoral lymph nodes in pancreatic cancer revisited; is it truly equivalent to lymph node metastasis?

Abstract

Pancreatic cancer is well-known for its devastating survival outcomes. Recently released statistics in the United States show that it is the 4th leading cause of cancer death in both males and females. 1,2 One of the major reasons for such an outcome is its tendency for early metastasis through lymphatic drainage. 3,4 Many studies have demonstrated the adverse effect of lymph node (LN) metastasis. [5][6][7][8][9] Thus, the importance of accurately reporting the LN status cannot be overemphasized for proper staging and more accurate prognosis prediction. 10,11 Various methods have been proposed in reporting LN status including simple presence of LN metastasis, number of metastatic LNs, LN ratio, and log odds of positive LNs. [9][10][11][12][13][14][15][16][17]

Rethinking the TNM Classification Regarding Direct Lymph Node Invasion in Pancreatic Ductal Adenocarcinoma

“…Our study provides data that support a redefinition of the N stage by including the mechanism of lymph node involvement [ 12 ]. We believe that this could lead to a more precise description of lymph node status, providing an individualized prognosis of PDAC patients compared with the current TNM classification.…”

“…Some groups have attempted to find the prognostic factors via lymph node mechanisms but have shown some contradictory data [ 7 , 8 , 9 , 10 , 11 , 12 ].…”

“…Lymph nodes were categorized according to the mechanism/presence of invasion: direct (Nc), metastasis (Nm), mixed mechanism (Ncm), and node-negative (N0). Nc was defined as direct lymph node invasion by the tumour ( Figure 1 A), Nm was defined as regional lymph node metastasis without any contact to the tumour ( Figure 1 B) as previously described [ 7 , 8 , 9 , 10 , 11 , 12 ], and Ncm was defined as a combination of both ( Figure 1 C). If discrepancies existed between the two pathologists, these were resolved by extensively discussing the case and if no consensus was met, the opinion of a third pathologist was asked.…”

“…The most powerful predictor of survival after surgery is lymph node status [ 3 , 4 , 5 , 6 ]. Previous studies [ 7 , 8 , 9 , 10 , 11 , 12 ] have analysed the mechanisms of lymph node invasion and compared the prognosis of direct lymph nodes from the main tumour through cancer related angiogenesis and immunosuppression via crosstalk between the cancer endothelium and the surrounding microenvironment and lymph node metastasis without any contact with the main tumour [ 13 , 14 ]. These small studies showed that the mechanisms underlying lymph node invasion may have effects on the survival rate, however, the data are contradictory [ 7 , 8 , 9 , 10 , 11 , 12 ].…”

“…Previous studies [ 7 , 8 , 9 , 10 , 11 , 12 ] have analysed the mechanisms of lymph node invasion and compared the prognosis of direct lymph nodes from the main tumour through cancer related angiogenesis and immunosuppression via crosstalk between the cancer endothelium and the surrounding microenvironment and lymph node metastasis without any contact with the main tumour [ 13 , 14 ]. These small studies showed that the mechanisms underlying lymph node invasion may have effects on the survival rate, however, the data are contradictory [ 7 , 8 , 9 , 10 , 11 , 12 ]. In addition, the latest TNM classification—the 8th edition of the American Joint Committee on Cancer (AJCC) with changes to the T and N categories—does not consider the mechanisms of lymph node involvement [ 15 , 16 , 17 , 18 , 19 ].…”